Purpose: :
Corneal disease-1 (Dstncorn1) mice are deficient for destrin,which depolymerizes filamentous actin (F-actin) into its monomericform. Dstncorn1 mice exhibit accumulation of F-actin in thecorneal epithelial cells, recruitment of inflammatory cellsto the cornea, epithelial cell hyperproliferation, and stromalneovascularization. In a previous study, we identified thatserum response factor (Srf) and 53 of its target genes are upregulatedin the cornea of Dstncorn1 mice. The purpose of this study wasto determine the role of SRF in the development of Dstncorn1phenotypes through conditional gene ablation specific to thecorneal epithelial cells.

Results: :
Injection of Doxycycline for 30 days demonstrated that conditionalablation of SRF expression in the corneal epithelium rescuesthe abnormalities observed in Dstncorn1 mice. In mice with thegenotype Dstncorn1/corn1 Srff/f Krt12rtTA/+TetO-cre+, the levelof F-actin is greatly reduced, as is the level of inflammatorycell infiltration. The number of proliferating cells is alsomarkedly decreased, and the pattern of cell proliferation resemblesthat of a normal cornea. Neovascularization is also less evident.

Conclusions: :
This study demonstrated that abnormal activation of SRF is primarilyresponsible for the corneal abnormalities observed in Dstncorn1mice. In particular, Srf was found to mediate the F-actin accumulation,inflammatory cell recruitment, hyperproliferation, and neovascularizationphenotypes in Dstncorn1 mice. This study also showed that theseabnormalities are due to SRF expression in the corneal epithelialcells, and demonstrated that the stromal phenotypes, inflammationand neovascularization, occur due to altered gene expressionin the corneal epithelium of Dstncorn1 mice.